Background: Epothilones have been reported to exhibit potent anticancer activity and a number of epothilone analogs have entered clinical evaluation in humans (in addition to Epo B), one of these (BMS-247550, ixabepilone) recently obtaining FDA approval as an anticancer drug. Most of the current potent epothilone analogues bear close structural resemblance to the parent compounds. However, compounds with more stringent structural modifications of the epothilone scaffold may produce new lead structures which altered pharmacological profiles for drug discovery. To this end, researchers at the University of Toledo have developed a new class of hypermodified conformationally restrained analogues of epothilones that may be used for the treatment against leukemia cell lines.

Invention description: Researchers at The University of Toledo deisgned and synthesized a new class of open chain and conformationally restrained analogues of anti-cancer agent epothilone and their use as anti-cancer agents in general. The researchers further demonstrated that some of the conformationally restrained analogues, so synthesized, showed very high selective activity against two leukemia cell lines in the NCI 60 cell line human tumor assay.One of these analogues specifically showed strong growth inhibitory activity on CCRF-CEM and SR leukemia cell lines with GI50 values of 2.7 and 2.9 nm, respectively. However, this compound did not show any significant activity on any of the other cell lines, including those derived from breast (MCF-7) and ovarian (SK-OV-3) cancers. This strategy may be further used to develop new lead molecules of varying pharmacological profile by substantial modification of the epothilone scaffold.

Applications: In treating Leukemia and other forms of cancer and development of new lead molecules as anti-cancer agents.